Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Cell Transplant. 2019 Sep-Oct;28(9-10):1161-1172. doi: 10.1177/0963689719842161. Epub 2019 Apr 22.
Vascular smooth muscle cells (VSMCs) play an important role after a subarachnoid hemorrhage (SAH). The changes in VSMCs following bexarotene treatment after SAH are unknown. In the present study, neurological impairment, decreased cerebral cortical blood flow and transformation of cerebral VSMCs from a contractile to a synthetic phenotype were observed after SAH. Bexarotene reduced neurological impairment, improved cerebral cortical blood flow, inhibited VSMC phenotypic transformation and suppressed the expression of 5-lipoxygenase-activating protein (FLAP) and leukotriene B4 (LTB), which was partly reversed by GW9662, an inhibitor of peroxisome proliferator-activated receptor gamma (PPARγ). Mechanistically, sh-PPARγ-mediated phenotypic transformation of VSMCs was partially suppressed by MK886, an antagonist of FLAP. Therefore, we conclude that bexarotene reduced neurological impairment, improved cerebral cortical blood flow and inhibited the VSMC phenotypic transformation after SAH, which was achieved by activating PPARγ-mediated inhibition of FLAP/LTB in VSMCs.
血管平滑肌细胞（VSMCs）在蛛网膜下腔出血（SAH）后起着重要作用。SAH 后贝沙罗汀治疗对 VSMCs 的影响尚不清楚。本研究观察到 SAH 后 VSMCs 表现出神经功能缺损、大脑皮质血流量减少以及从收缩型向合成型表型的转化。贝沙罗汀可减轻神经功能缺损，改善大脑皮质血流量，抑制 VSMC 表型转化，抑制 5-脂氧合酶激活蛋白（FLAP）和白三烯 B4（LTB）的表达，而 PPARγ 抑制剂 GW9662 可部分逆转这种作用。机制上，FLAP 的拮抗剂 MK886 部分抑制了 sh-PPARγ 介导的 VSMC 表型转化。因此，我们得出结论，贝沙罗汀通过激活 PPARγ 介导的 VSMCs 中 FLAP/LTB 的抑制作用，减轻 SAH 后的神经功能缺损，改善大脑皮质血流量，并抑制 VSMC 表型转化。
